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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
HLArestrictor-a tool for patient-specific predictions of HLA restriction elements and optimal epitopes within peptides
Immunogenetics, Volume 63, No. 1, Year 2011
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Description
Traditionally, T cell epitope discovery requires considerable amounts of tedious, slow, and costly experimental work. During the last decade, prediction tools have emerged as essential tools allowing researchers to select a manageable list of epitope candidates to test from a larger peptide, protein, or even proteome. However, no current tools address the complexity AR caused by the highly polymorphic nature of the restricting HLA molecules, which effectively individualizes T cell responses. To fill this gap, we here present an easy-to-use prediction tool named HLArestrictor ( http://www.cbs.dtu.dk/ services/HLArestrictor ), which is based on the highly versatile and accurate NetMHCpan predictor, which here has been optimized for the identification of both the MHC restriction element and the corresponding minimal epitope of a T cell response in a given individual. As input, it requires high-resolution (i.e., 4-digit) HLA typing of the individual. HLArestrictor then predicts all 8-11mer peptide binders within one or more larger peptides and provides an overview of the predicted HLA restrictions and minimal epitopes. The method was tested on a large dataset of HIV IFNγ ELIspot peptide responses and was shown to identify HLA restrictions and minimal epitopes for about 90% of the positive peptide/patient pairs while rejecting more than 95% of the negative peptide-HLA pairs. Furthermore, for 18 peptide/HLA tetramer validated responses, HLArestrictor in all cases predicted both the HLA restriction element and minimal epitope. Thus, HLArestrictor should be a valuable tool in any T cell epitope discovery process aimed at identifying new epitopes from infectious diseases and other disease models. © 2010 Springer-Verlag.
Authors & Co-Authors
Erup Larsen, Malene
Denmark, Lyngby
Technical University of Denmark
Kløverpris, Henrik N.
United Kingdom, Oxford
Nuffield Department of Medicine
Stryhn, Anette
Denmark, Copenhagen
Det Sundhedsvidenskabelige Fakultet
Koofhethile, Catherine Kegakilwe
United Kingdom, Oxford
Nuffield Department of Medicine
Sims, Stuart
United Kingdom, Oxford
Nuffield Department of Medicine
Ndung'u, Thumbi P.
South Africa, Durban
University of Kwazulu-natal
United States, Cambridge
Harvard University
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
Nuffield Department of Medicine
Buus, Soren
Denmark, Copenhagen
Det Sundhedsvidenskabelige Fakultet
Nielsen, Morten
Denmark, Lyngby
Technical University of Denmark
Statistics
Citations: 57
Authors: 9
Affiliations: 5
Identifiers
Doi:
10.1007/s00251-010-0493-5
ISSN:
00937711
e-ISSN:
14321211
Research Areas
Health System And Policy
Infectious Diseases